The Inorganic Nitrate and eXercise Performance in Heart Failure (iNIX-HF) -a Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 75
- 试验地点
- 2
- 主要终点
- VO2 Peak Testing
研究概览
简要总结
The goals of this project are to determine the effectiveness of acute (2 hours after a single dose) and chronic (after 6 weeks of once-a-day dosing) KNO3 treatment (10mmol) vs. placebo on quadriceps muscle power and on aerobic exercise performance (V̇O2peak) in patients with HFrEF (left ventricular ejection fraction <45%). The investigators hypothesize that both acute and chronic dosing of 10mmol of KNO3 will improve exercise performance in HFrEF. To test this hypothesis, the investors will perform a randomized, double-blind, placebo-controlled, parallel-arm design study.
详细描述
Visit 1 - Screening
Visit 1 will be considered the screening visit. Participants will not be required to fast for this visit. This visit will be conducted over approximately 1.5 to 2 hours. The following procedures will be completed during this visit:
- Informed consent, if not already obtained previously.
- Health questionnaire
- Review of medical history and concomitant medication usage
- Review of any patient reported eligibility criteria (e.g., agreeance to using birth control, not using phosphodiesterase, inhibitors, etc.)
- Labs
a. As this is the only blood sample collected during this visit, IV placement is not necessary at this visit. 6. Urine pregnancy test 7. Physical examination 8. NYHA classification 9. Vital signs measurements 10. Height and weight measurements 11. Resting TTE with or without contrast
At the conclusion of Visit 1, eligibility criteria for each participant will be reviewed and confirmed by the PI prior to the participant completing Visit 2 procedures.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Double blind, placebo controlled
入排标准
- 年龄范围
- 19 Years 至 79 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •To participate in this study, a patient must meet all of the criteria listed below:
- •Males and females aged greater than or equal to 18y and less than 80y at time of consent
- •Diagnosis of heart failure with reduced ejection fraction
- •New York Heart Association (NYHA) Class II-III at Visit 1
- •Ejection fraction less than 45%, as evaluated through transthoracic echocardiography at Visit 1
- •Stable medical therapy, defined by no addition or removal (or change of more than 100 percent) of the following for 60 days prior to Visit 1: beta-adrenergic blockade and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blocker (ARB or aldosterone antagonists) or ARNI (ARB + sacubitril)
- •Ability and willingness to sign an IRB approved written informed consent form; legally authorized representatives are not allowed in this study
排除标准
- •To participate in this study, a patient must not meet any of the criteria listed below:
- •Vulnerable populations as defined by the U.S. Department of Health and Human Services; prisoners and children will be excluded from this study
- •Pharmacologic, organic nitrate therapy within 3 months prior to Visit 1
- •Major orthopedic, psychiatric, neurological, or other conditions that would hinder the ability to complete the exercise tests at the time of Visit 1
- •Estimated glomerular filtration rate less than 45 mL/min/1.73m2 on screening clinical laboratories measured at Visit 1
- •Systolic blood pressure less than 90mmHg or greater than 180mmHg at Visit 1
- •Diastolic blood pressure less than 40mmHg or greater than 100mmHg at Visit 1
- •Previous adverse reaction to nitrate prior to Visit 1
- •Treatment with phosphodiesterase inhibitors within the last 3 months prior to Visit 1; Patient must also be willing to not take them for the duration of the trial
- •Diagnosis of primary hypertrophic cardiomyopathy, infiltrative cardiomyopathy (e.g., amyloid), active myocarditis, or complex congenital heart disease prior to Visit 1
- •Active collagen vascular disease at time of Visit 1
- •Percutaneous coronary intervention, new bi-ventricular pacing, or coronary artery bypass grafting within the 3 months prior to Visit 1
- •Valvular heart disease with severe regurgitation or stenosis of any valve, as demonstrated on the echocardiogram at Visit 1
- •Known severe liver disease as evidenced by encephalopathy or variceal bleeding;
- •Terminal disease (other than heart failure) with expected survival less than 1 y at time of Visit 1
- •Enrollment in another therapeutic trial at time of Visit 1
- •Pregnant and breastfeeding women or postmenopausal women taking exogenous estrogen replacement therapy at time of Visit 1
- •To meet this criterion, patients must have a negative urine pregnancy test and provide verbal confirmation that they are not breastfeeding at time of Visit
- •Note, post-menopausal is defined as last menstrual period occurring greater than or equal to 12 months prior to Visit 1 or confirmation of prior bilateral oophorectomy at least 6 months prior to first dose of study drug.
- •Women of childbearing potential or men with childbearing potential partners must agree that the participant and/or their partner will use at least two of the following highly effective method of birth control from study entry until 48 hours after completing study therapy, if not abstaining from sexual activity:
- •Barrier method contraception (e.g., male or female condoms with or without a spermicidal agent, diaphragm, or cervical cap with spermicide)
- •Stable dose of injectable, depot, oral, implanted, intravaginal, or transdermal hormonal contraception for at least 30 days before sexual activity
- •Intrauterine device (IUD) with or without hormones
- •Surgical sterilization
- •For women, this includes hysterectomy, bilateral oophorectomy with or without hysterectomy, or bilateral tubal ligation, bilateral salpingectomy, completed at least 6 months before first dose of study drug.
- •For men, this includes vasectomy.
- •Patients requiring exogenous oxygen at rest or during exercise prior to Visit 1
- •Patients with active angina at time of Visit 1 or ischemia due to epicardial coronary disease prior to or at time of Visit 1
- •Patients taking xanthine oxidase inhibitors at time of Visit 1
- •Individuals taking proton pump inhibitors and/or antacids at time of Visit 1, if unable to stop these medications for the duration of the study.
- •Note, while patients will be asked to refrain from taking these medications for the duration of the study, they may take tums. However, patients must discontinue Tums for 5 days prior to study visits 2, 3, and 4.
研究组 & 干预措施
Potassium Nitrate (KNO3) treatment arm
10 mmol of KNO3 via a single gel capsule to be consumed orally once per day for 6 weeks.
干预措施: KNO3 (Drug)
Placebo-controlled arm
10 mmol of placebo via a single gel capsule to be consumed orally once per day for 6 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
VO2 Peak Testing
时间窗: Determined at Visit 1, Visit 2, and Visit 3, which will be scheduled throughout 8 weeks.
peak oxygen consumption during treadmill exercise
Maximal muscle power
时间窗: Determined at Visit 1, Visit 2, and Visit 3, which will be scheduled throughout 8 weeks.
assessment of quadriceps power
VO2 Peak Testing
时间窗: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
peak oxygen consumption during treadmill exercise
Maximal muscle power
时间窗: Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.
assessment of quadriceps power
次要结局
- Maximal muscle velocity(Determined at Visit 1, Visit 2, and Visit 3, which will be scheduled throughout 8 weeks.)
- Maximal exercise time on treadmill(Determined at Visit 1, Visit 2, and Visit 3, which will be scheduled throughout 8 weeks.)
- Breath nitric oxide (NO) level(Determined at Visit 1, Visit 2, and Visit 3, which will be scheduled throughout 8 weeks.)
- MLHFQ questionnaire(Determined at Visit 1, Visit 2, and Visit 3, which will be scheduled throughout 8 weeks.)
- KCCQ questionnaire(Determined at Visit 1, Visit 2, and Visit 3, which will be scheduled throughout 8 weeks.)
- Plasma nitrate and nitrite(Determined at Visit 1, Visit 2, and Visit 3, which will be scheduled throughout 8 weeks.)
- MLHFQ questionnaire(Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.)
- KCCQ questionnaire(Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.)
- Maximal muscle velocity(Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.)
- Maximal exercise time on treadmill(Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.)
- Plasma nitrate and nitrite(Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.)
- Breath nitric oxide (NO) level(Determined at Baseline visit, Acute Dose Visit, and Chronic Dose Visit, which will be scheduled throughout 8 weeks.)